DESCRIPTION: This is an application for a Clinical Research Unit (CRU) to participate in a 6-year, cooperative, multi-center study which will evaluate whether combining effective pharmacological and behavioral treatments will improve treatment outcomes for alcohol dependence. The multi-center study proposes that at least 800 Subjects with a DSM-IV diagnosis of alcohol dependence will be recruited from a minimum of 5 sites. The study will be an 8-cell design (100 Ss per cell), crossing 4 medication/placebo groups with 2 behavioral treatments, one of which is required to be a Project MATCH treatment, and the other is to be a less intensive intervention, adaptable to managed care settings. One medication will be 50mg/day naltrexone (NAL), FDA-approved in the US for alcohol dependence, and the second will be 2.0g/day acamprosate (ACP), shown in 1 1 of 12 European randomized trials to sustain abstinence at a higher rate than Subjects treated with placebo (PLA). These medications will be given alone, or in combination, and compared to PLA. For the more intensive behavioral intervention, we will use Project MATCH's Cognitive Behavioral Coping Skills Therapy (CBT). For the less intensive intervention, we propose to augment or enhance simple medication management (advice and support) with motivational interviewing strategies and teaching Subjects treatment compliance techniques. We developed a manual that we have used successfully for over 2 years at our Center which emphasizes compliance enhancement techniques; hence, we refer to the intervention as CET. S recruitment will be through community and professional referrals from the Philadelphia area to the outpatient Treatment Research Center (TRC) at the University of Pennsylvania. Over a 2-year period, our TRC site will randomly assign 160 DSM-IV alcohol dependent Subjects (80 Subjects per yr) to one of four medication groups and one of two behavioral intervention groups. That is, each S will receive one of eight possible treatments for 24 weeks -- ACP-PLA-CET, NAL-PLA-CET, ACP-NAL-CET, PLA-PLA-CET, , ACP-PLA-CBT, NAL-PLA-CBT ACP-NAL-CBT, or PLA-PLA-CBT. After the treatment trial, there will be four follow-up visits at 9- 12- 15- and 18-months post-treatment entry. This application also includes a 1-year preliminary study that will evaluate it low-intensity CET would be suitable as the less intensive intervention in the multi-center study. Our current practice has been to deliver CET in weekly visits with excellent medication compliance rates as high as 88.2 percent. The preliminary study will investigate whether we can achieve good compliance and outcome rates with fewer than weekly visits in a 12-week period. There will be 80 DSM-IV alcohol dependent Subjects prescribed (open-label) 50mg/day NAL who will be randomly assigned to receive CET either for 12 (weekly) visits, or for 4 strategically-spaced visits over 12 weeks. Results will inform us whether a low-intensity CET can be given alone with effective medication without significant reductions in compliance and good outcome rates. It also will inform us of the impact enhanced medication management practices have on treatment compliance and outcome rates in the absence of other types of behavioral interventions. In both studies, Subjects will be assessed with measures of provide self-reports and lab specimens at each research visit. Therapeutic process will be assessed with measures of compliance (via MEMS caps, pill counts and blood levels), motivation (URICA), therapeutic alliance (WAI), and the acquisition of coping skills (ASRPT).